Neurorehabilitation and neural repair最新文献

Background: There is an increasing need for motor assessments after stroke that can be performed quickly and remotely. The Fast Outcome Categorization of the Upper Limb after Stroke-4 (FOCUS-4) assessment remotely classifies upper limb outcome into 1 of 4 categories after stroke and was developed via retrospective analysis of Action Research Arm Test (ARAT) scores.

Objective: The aim of this study was to prospectively evaluate the accuracy and reliability of FOCUS-4 assessments for categorizing upper limb outcome after stroke when administered remotely during a videocall compared to an in-person ARAT.

Methods: Data were collected from 26 participants at 3 months post-stroke (3M), 27 participants at 6 months post-stroke (6M), and 56 participants at the chronic stage of stroke (>6M). Participants performed an in-person ARAT and a remote FOCUS-4 assessment administered during a videocall, and accuracy was evaluated by comparing the upper limb outcome categories. Participants at the chronic stage of stroke also performed a second remote FOCUS-4 assessment to assess between-day reliability.

Results: Overall accuracy of the remote FOCUS-4 assessment was 88% at 3M and 96% at 6M. Overall accuracy of the first and second remote FOCUS-4 assessments at the chronic stage was 75% and 79%, respectively. Reliability of the FOCUS-4 assessment at the chronic stage was 82%. The remote FOCUS-4 assessment was most accurate and reliable for participants with mild or severe upper limb functional impairment.

Conclusions: The remote FOCUS-4 assessment has potential to classify upper limb functional capacity or to screen possible participants for stroke trials, but external validation is required.

Background: Anodal transcranial direct current stimulation (AtDCS), a neuromodulatory technique, has been applied to treat traumatic brain injury (TBI) in patients and was reported to promote functional improvement. We evaluated the effect of contralesional AtDCS on axonal sprouting of the intact corticospinal tract (CST) and the underlying mechanism in a TBI mouse model to provide more preclinical evidence for the use of AtDCS to treat TBI.

Methods: TBI was induced in mice by a contusion device. Then, the mice were subjected to contralesional AtDCS 5 days per week followed by a 2-day interval for 7 weeks. After AtDCS, motor function was evaluated by the irregular ladder walking, narrow beam walking, and open field tests. CST sprouting was assessed by anterograde and retrograde labeling of corticospinal neurons (CSNs), and the effect of AtDCS was further validated by pharmacogenetic inhibition of axonal sprouting using clozapine-N-oxide (CNO).

Results: TBI resulted in damage to the ipsilesional cortex, while the contralesional CST remained intact. AtDCS improved the skilled motor functions of the impaired hindlimb in TBI mice by promoting CST axon sprouting, specifically from the intact hemicord to the denervated hemicord. Furthermore, electrical stimulation of CSNs significantly increased the excitability of neurons and thus activated the mechanistic target of rapamycin (mTOR) pathway.

Conclusions: Contralesional AtDCS improved skilled motor following TBI, partly by promoting axonal sprouting through increased neuronal activity and thus activation of the mTOR pathway.

Background: Rest-activity rhythm (RAR) is a modifiable behavioral factor associated with affect and cognition. Identifying RAR characteristics associated with affect and cognition among stroke survivors provides insight into preventing poststroke affective and cognitive impairment.

Objective: To examine the associations of RAR characteristics with affect and cognition among community-dwelling stroke survivors.

Methods: Forty participants with mild stroke (mean age = 52.8; 42.5% female; 55% White) reported their affect and cognitive complaints using ecological momentary assessment and wore an accelerometer for 7 consecutive days and completed the National Institutes of Health Toolbox Cognition Battery. RAR characteristics were extracted using parametric and non-parametric approaches. Multivariable linear regressions were used to identify RAR characteristics associated with affect and cognition.

Results: Later onset of rest (B = 0.45; P = .008) and activity (B = 0.36; P = .041) were positively associated with depressed affect. These associations were reversed for cheerful effect (rest onset: B = -0.42; P = .017; activity onset: B = -0.39; P = .033). Cheerful affect was also positively associated with relative amplitude (ie, distinctions in activity levels between rest and activity; B = .39; P = .030). Intra-daily variability (ie, RAR fragmentation; B = 0.35; P = .042) and later onset of activity (B = .36; P = .048) were positively associated with cognitive complaints. Less erratic RAR was positively associated with fluid cognition (B = 0.29; P = .036); RAR fragmentation was positively associated with crystallized cognition (B = 0.39; P = .015).

Conclusions: We identified RAR correlates of affect and cognition among stroke survivors, highlighting the value of managing RAR and sleep in stroke rehabilitation. Future studies should test whether advancing the onset of rest and activity, promoting a regular active lifestyle, and improving rest and sleep in the nighttime protect stroke survivors from affective and cognitive impairment.

Background: Caloric restriction promotes neuroplasticity and recovery after neurological injury. In mice, we tested the hypothesis that caloric restriction can act post-stroke to enhance training-associated motor recovery.

Methods: Mice were trained to perform a skilled prehension task. We then induced a photothrombotic stroke in the caudal forelimb area, after which we retrained animals on the prehension task following an 8-day delay. Mice underwent either ad libitum feeding or alternate day fasting beginning 1-day after stroke and persisting for either 7 days or the entire post-stroke training period until sacrifice.

Results: Prior studies have shown that post-stroke recovery of prehension can occur if animals receive rehabilitative training during an early sensitive period but is incomplete if rehabilitative training is delayed. In contrast, we show complete recovery of prehension, despite a delay in rehabilitative training, when mice underwent alternate day fasting beginning 1-day post-stroke and persisting for either 7 days or the entire post-stroke training period until sacrifice. Recovery was independent of weight loss. Stroke volumes were similar across groups.

Conclusions: Post-stroke caloric restriction led to recovery of motor function independent of a protective effect on stroke volume. Prehension recovery improved even after ad libitum feeding was reinstituted suggesting that the observed motor recovery was not merely a motivational response. These data add to the growing evidence that post-stroke caloric restriction can enhance recovery.

Background: Cerebellum shares robust di-synaptic dentato-thalamo-cortical (DTC) connections with the contralateral motor cortex. Preclinical studies have shown that DTC are excitatory in nature. Structural integrity of DTC is associated with better upper extremity (UE) motor function in people with stroke, indicating DTC are important for cerebellar influences on movement. However, there is a lack of understanding of physiologic influence of DTC in humans, largely due to difficulty in accessing the dentate nucleus.

Objective: Characterize DTC physiology using dentate nucleus deep brain stimulation (DBS) combined with transcranial magnetic stimulation (TMS) in stroke.

Methods: Nine chronic stroke survivors with moderate-to-severe UE impairment (Fugl-Meyer 13-38) underwent a paired DBS-TMS experiment before receiving experimental dentate nucleus DBS in our first-in-human phase I trial (Baker et al., 2023, Nature Medicine). Conditioning DBS pulses were given to dentate nucleus 1 to 10 ms prior to supra-threshold TMS pulses given to ipsilesional motor cortex. Effects were assessed on motor evoked potentials (MEPs). Size of DBS-conditioned MEPs was expressed relative to TMS MEPs, where values >1 indicate facilitation.

Results: Dentate nucleus DBS led to facilitation of MEPs at short-latency intervals (3.5 and 5 ms, P = .049 and .021, respectively), a phenomenon we have termed dentato-cortical facilitation (DCF). Higher DCF was observed among patients with more severe UE impairment. Diffusion tensor imaging revealed microstructure of thalamo-cortical portion of DTC was related to higher corticomotor excitability.

Conclusions: Our in vivo investigation reveals for the first time in humans the intrinsic excitatory properties of DTC, which can serve as a novel therapeutic target for post-stroke motor recovery.

Background: Post-stroke depression (PSD) is a frequent psychiatric complication, however very few studies have investigated its relation to the affected upper extremity (UE) post-stroke. Objective. To compare the affected UE in terms of motor impairment, functional ability, and daily-use in individuals with and without PSD during the first 6 months post-stroke.

Methods: This study analyzed data from a previous cohort; participants were assessed at rehabilitation admission (T1), 6 weeks (T2), and 6 months (T3) post-stroke. At each time point we compared between participants with and without PSD (Geriatric Depression Scale score ≥ 5). The Fugl-Meyer Motor Assessment assessed motor impairment, Action Research Arm Test assessed functional ability, and the Rating of Everyday Arm-Use in the Community and Home assessed daily-use. Independence in daily activities and cognition were also assessed.

Results: A total of 116 participants were recruited, 38% had PSD at T1. No significant differences were found between groups at T1 and T2. However, significant differences (z = -5.23 to -2.66, p < .01) were found between groups for all UE measures at T3; participants with PSD had lower motor and functional ability and less daily hand-use than participants without PSD. At T3 participants with PSD were also less independent in daily-living.

Conclusions: PSD is associated with greater UE motor, functional, and daily-use disability at 6 months post-stroke. Our findings underscore the negative impact of PSD on UE during the crucial transition period when individuals return home and integrate back into the community. Further research is needed to delineate the effect of change in PSD status on UE outcomes post stroke.

Background: Gait characteristics and their changes during the 6-minute walking test (6MWT) in people with multiple sclerosis (pwMS) have been described in the literature, which one may refer to as walking fatigability in the body function level of the International Classification of Functioning, Disability, and Health. However, whether these metrics are reliable is unknown.

Objective: To investigate the between-day reliability of the gait characteristics and their changes in pwMS and healthy controls (HCs).

Methods: Forty-nine pwMS (EDSS 4.82 ± 1.22 and 54.7 ± 9.36 years) and 23 HCs (50.6 ± 6.1 years) performed the 6MWT, as fast as possible but safely while wearing Inertial Measurement Units. Gait characteristics were measured in the pace, rhythm, variability, asymmetry, kinematics, coordination, and postural control domains and were obtained in intervals of 1 minute during the 6MWT. In addition, gait characteristics change in the last minute compared with the first minute were calculated for all gait variables using a fatigability index (ie, distance walking index). The intraclass correlation coefficient (ICC), Bland-Altman Plots, and Standard error of measurement were applied to investigate reliability.

Results: Reliability of gait characteristics, minute-by-minute, and for their changes (ie, using the fatigability index) ranged from poor to excellent (pwMS: ICC 0.46-0.96; HC: ICC 0.09-0.97 and pwMS: ICC 0-0.72; HC: ICC 0-0.77, respectively).

Conclusion: Besides coordination, at least 1 variable of each gait domain showed an ICC of moderate or good reliability for gait characteristics changes in both pwMS and HC. These metrics can be incorporated into future clinical trials and research on walking fatigability.Clinical Trial Registration: NCT05412043.

Background: Parkinson's disease can negatively affect vocal functioning and social wellbeing, particularly in the latter stages of disease progression. Face-to-face group singing interventions can improve communication and wellbeing outcomes, yet not all people can access in-person sessions. To help overcome barriers to participation, exploration of the feasibility and utility of online therapeutic singing programs is needed.

Objectives: To evaluate the feasibility, acceptability, and preliminary efficacy of a 12-week ParkinSong Online intervention on speech and wellbeing for people with Parkinson's disease.

Methods: A total of 28 participants with idiopathic Parkinson's disease were recruited to a single-arm feasibility study. Weekly 90-minute online sessions were co-facilitated by a music therapist and speech pathologist. Speech and wellbeing assessments were conducted pre and post intervention. Participant and facilitator surveys were administered after each session, with focus group interviews at the end of the program.

Results: The recruitment rate was high (90%) with no attrition, adverse events, or safety issues. There was good intervention fidelity, attendance (average 89%), and positive participant experience. Feasibility was good, with technology reported as the main challenge (connecting and navigating Zoom). No improvements were seen in voice measures or wellbeing outcomes in this small trial. The online format used in this study did not provide the same benefits as in-person ParkinSong sessions.

Conclusions: ParkinSong Online is feasible for recreational purposes and social engagement provided that people have adequate technological knowledge or support. The optimal online delivery format to achieve communication improvements in Parkinson's awaits confirmation.

Background: The aim of the International Stroke Recovery and Rehabilitation Alliance is to create a world where worldwide collaboration brings major breakthroughs for the millions of people living with stroke. A key pillar of this work is to define globally relevant criteria for centers that aspire to deliver excellent clinical rehabilitation and generate exceptional outcomes for patients.

Objectives: This paper presents consensus work conducted with an international group of expert stroke recovery and rehabilitation researchers, clinicians, and people living with stroke to identify and define criteria and measurable indicators for Centers of Clinical Excellence (CoCE) in stroke recovery and rehabilitation. These were intentionally developed to be ambitious and internationally relevant, regardless of a country's development or income status, to drive global improvement in stroke services.

Methods: Criteria and specific measurable indicators for CoCE were collaboratively developed by an international panel of stroke recovery and rehabilitation experts from 10 countries and consumer groups from 5 countries.

Results: The criteria and associated indicators, ranked in order of importance, focused upon (i) optimal outcome, (ii) research culture, (iii) working collaboratively with people living with stroke, (iv) knowledge exchange, (v) leadership, (vi) education, and (vii) advocacy. Work is currently underway to user-test the criteria and indicators in 14 rehabilitation centers in 10 different countries.

Conclusions: We anticipate that use of the criteria and indicators could support individual organizations to further develop their services and, more widely, provide a mechanism by which clinical excellence can be articulated and shared to generate global improvements in stroke care.